ArticleCancer causes & control : CCC2015
Insulin receptor variants and obesity-related cancers in the Framingham Heart Study.
Article in Cancer causes & control : CCC, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- METS-IR and all-cause mortality in Korean over 60 years old: Korean genome and epidemiology study-health examinees (KoGES-HEXA) cohorts.Frontiers in endocrinology · 2024Article
- Identifying the Antitumor Effects of Curcumin on Lung Adenocarcinoma Using Comprehensive Bioinformatics Analysis.Drug design, development and therapy · 2022Article
- Insulin receptor is implicated in triple-negative breast cancer by decreasing cell mobility.Journal of biomedical research · 2020Article
- The effects of genetic variants related to insulin metabolism pathways and the interactions with lifestyles on colorectal cancer risk.Menopause (New York, N.Y.) · 2019Observational
- A comprehensive analysis of polymorphic variants in steroid hormone and insulin-like growth factor-1 metabolism and risk of in situ breast cancer: Results from the Breast and Prostate Cancer Cohort Consortium.International journal of cancer · 2018Article
- Genetic Variants in Metabolic Signaling Pathways and Their Interaction with Lifestyle Factors on Breast Cancer Risk: A Random Survival Forest Analysis.Cancer prevention research (Philadelphia, Pa.) · 2018Article
- Article
- Insulin, insulin receptors, and cancer.Journal of endocrinological investigation · 2016Review
- Novel genetic risk factors for asthma in African American children: Precision Medicine and the SAGE II Study.Immunogenetics · 2016Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
purposeThe insulin-signaling pathway plays a pivotal role in cancer biology; however, evidence of genetic alterations in human studies is limited. This case-control study nested within the Framingham Heart Study (FHS) examined the association between inherited genetic variation in the insulin receptor (INSR) gene and obesity-related cancer risk.
methodsThe study sample consisted of 1,475 controls and 396 cases from the second familial generation of the FHS. Participants who provided consent were genotyped. Nineteen single-nucleotide polymorphisms (SNPs) in the INSR gene were investigated in relation to risk of obesity-related cancers combined and breast, prostate and colorectal cancers. Generalized estimation equation models controlling for familial correlations and include age, sex, smoking and body mass index as covariates, assuming additive models, were used.
resultsThree SNPs, rs2059807, s8109559 and rs919275, were significantly associated with obesity-related cancers (p value < 0.02) with the most significantly associated SNP being rs2059807 (p value = 0.008). Carriers of two copies of SNP rs2059807 risk allele T were significantly less prevalent among subjects with obesity-related cancers [f(TT)cases = 14 vs. f(TT)controls = 18 %; OR 1.23]. In exploratory analyses evaluating site-specific cancers, the INSR rs2059807 association with these cancers was consistent with that observed for the main outcome (ORs colorectal cancer = 1.5, breast cancer = 1.29, prostate = 1.06). There was no statistically significant interaction between the INSR-SNP and blood glucose in relation to obesity-related cancer.
conclusionsThe INSR gene is implicated in obesity-related cancer risk, as 3 of 19 SNPs were nominally associated, after false discovery rate (FDR) correction, with the main outcome. Risk allele homozygotes (rs2059807) were less prevalent among subjects with obesity-related cancer. These results should be replicated in other populations to confirm the findings.
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